Protein design has long been known to be a difficult task if for no other reason than the combinatorial explosion of possible molecules that constitute searchable sequence space. The sequence space of proteins is immense and is impossible to explore exhaustively using methods currently known in the art, which are often limited by the time and cost required to identify useful polypeptides. Part of the problem arises from the great number of polypeptide variants that must be sequenced, screened and assayed. Directed evolution methods increase the efficiency in honing in on the candidate biomolecules having advantageous properties. Today, directed evolution of proteins is dominated by various high throughput screening and recombination formats, often performed iteratively.
Various computational techniques have also been proposed for exploring sequence-activity space. Relatively speaking, these techniques are in their infancy and significant advances are still needed. Accordingly, new methods for improving the efficiency of screening, sequencing, and assaying candidate biomolecules are highly desirable.